““Epigenetics” refers to covalent modification of DNA, protein, or
RNA, resulting in changes to the function and/or regulation of these molecules, without altering
their primary sequences.” The Greek
prefix “epi” means “on top of” or “above”, so epigenetics literally means
regulation above the level of genetic mechanisms. In some cases, epigenetic
modifications are passed on to future generations, but in other instances they
are dynamic and change in response to environmental stimuli. Nearly every
aspect of biology is influenced by epigenetics, making it one of the most
important fields in science.
The importance of nature versus nurture has long been
disputed. It cannot be denied that environment greatly influences how a child
grows and develops, nor can it be denied that our DNA is the blueprint that
makes us who we are. Epigenetics merges these two seemingly contradictory lines
of thought to explain how environmental factors cause physical modifications to
DNA and its associated structures, which result in altered functions.
The big difference between genetic and epigenetic regulation
is that epigenetic mechanisms do not involve a change to the DNA sequence,
whereas genetic mechanisms involve the primary DNA sequence and changes or
mutations to this sequence. Epigenetic
regulation involves the modification of DNA and the proteins associated with
DNA, which results in changes to the conformation of DNA and accessibility of
other factors to DNA, without a change to the sequence of the DNA. As more
factors influencing heredity are discovered, today’s scientists are using
epigenetics to decipher the roles of DNA, RNA, proteins, and environment in
inheritance. The future of epigenetics will reveal the complexities of cellular
differentiation, embryology, the regulation of gene expression, aging, cancer,
and other diseases.
The most widely known epigenetic modification is DNA
methylation, which is a chemical process that adds a methyl group to DNA. It is
highly specific and always happens in a region in which a cytosine nucleotide
is located next to a guanine nucleotide that is linked by a phosphate; this is
called a CpG site (Egger et al., 2004; Jones & Baylin, 2002; Robertson,
2002). CpG sites are methylated by one of three enzymes called DNA
methyltransferases (DNMTs) (Egger et al., 2004; Robertson, 2002). Inserting methyl
groups changes the appearance and structure of DNA, modifying a gene's
interactions with the machinery within a cell's nucleus that is needed for
transcription. DNA methylation is used in some genes to differentiate which
gene copy is inherited from the father and which gene copy is inherited from
the mother, a phenomenon known as imprinting.
The first human disease to be linked to epigenetics was
cancer in 1983. Researchers found that diseased tissue from patients with
colorectal cancer had less DNA methylation than normal tissue from the same
patients (Feinberg & Vogelstein, 1983). Because methylated genes are
typically turned off, loss of DNA methylation can cause abnormally high gene
activation by altering the arrangement of chromatin. On the other hand, too
much methylation can undo the work of protective tumor suppressor genes. CpG
islands become excessively methylated in cancer cells, thereby causing genes
that should not be silenced to turn off. This abnormality is the trademark
epigenetic change that occurs in tumors and happens early in the development of
cancer (Egger et al., 2004; Robertson, 2002; Jones & Baylin, 2002).
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